We have explored ways of directing liposomes to particular target cells or tissues. When hapten-modified human lymphocytes were incubated with hapten-modified liposomes and the corresponding bivalent antibody, liposomes bound in large numbers to the cell surface. However, contents of the bound vesicles did not enter the cells. When murine myeloma cells were incubated with liposomes carrying the appropriate hapten, again there was binding but no delivery of liposome contents into the cells. When methotrexate (MTX) was encapsulated in such vesicles, hapten-specific binding to the cell surface did not result in entry into the cell and inhibition of its metabolism. We are currently extending these studies to phagocytic cell lines. We have designed "temperature-sensitive" liposomes that release an entrapped drug locally at temperatures obtainable by mild hyperthermia, for example in the treatment of tumors. In the presence of serum the ration of drug release at 43 degrees to that at 37 degrees can be made greater than 100.1. We find that (i) such liposomes deliver more than 10 times as much MTX to heated murine tumors as to unheated control tumors, (ii) the drug reaches its target enzyme in the tumor cell cytoplasm and (iii) tumor growth can thus be delayed.